4-[(2,4-二氯-5-甲氧基苯基)氨基]-7-氟-6-甲氧基-3-喹啉甲腈 | 622369-46-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 4-[(2,4-二氯-5-甲氧基苯基)氨基]-7-氟-6-甲氧基-3-喹啉甲腈
• 中文别名: 4-(2,4-二氯-5-甲氧基苯胺基)-7-氟-6-甲氧基-3-喹啉甲腈；4-(2,4-二氯-5-甲氧基苯氨)-7-氟-6-甲氧基喹啉-3-腈
• 英文名称: 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile
• 英文别名: 4-(2,4-dichloro-5-methoxyphenylamino)-7-fluoro-6-methoxyquinoline-3-carbonitrile；4-(2,4-dichloro-5-methoxyanilino)-7-fluoro-6-methoxyquinoline-3-carbonitrile
• CAS: 622369-46-4
• 化学式: C₁₈H₁₂Cl₂FN₃O₂
• 分子量: 392.217
• InChiKey: AXSYHFQBQMKSGH-UHFFFAOYSA-N

物化性质

• 熔点：
  219-221℃

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2933499090

反应信息

• 作为反应物：
  描述：

  N-(3-氨丙基)吗啉 、 4-[(2,4-二氯-5-甲氧基苯基)氨基]-7-氟-6-甲氧基-3-喹啉甲腈 以 N-甲基吡咯烷酮 为溶剂， 反应 29.0h， 以59%的产率得到4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[(3-morpholin-4-ylpropyl)amino]quinoline-3-carbonitrile
  参考文献：
  名称：

  Facile preparation of new 4-phenylamino-3-quinolinecarbonitrile Src kinase inhibitors via 7-fluoro intermediates: Identification of potent 7-amino analogs

  摘要：

  A more efficient preparation of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (2), the penultimate intermediate in the synthesis of bosutinib (1a), was developed. New 7-alkoxy-4-phenylamino-3-quinolinecarbonitrile Src inhibitors were prepared from 5 and 9, the 6-ethoxy and 6-hydrogen analogs of 2. In addition, the fluoro group of 2 was readily displaced by primary and secondary amines to give 7-amino analogs. Two of these 7-amino analogs, 15 and 18, were potent Src inhibitors with in vivo activity. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.09.028
• 作为产物：
  描述：

  3-氟-4-甲氧基苯胺 在 吡啶盐酸盐 、 三氯氧磷 作用下， 以 乙二醇乙醚 、 甲苯 为溶剂， 反应 8.0h， 生成 4-[(2,4-二氯-5-甲氧基苯基)氨基]-7-氟-6-甲氧基-3-喹啉甲腈
  参考文献：
  名称：

  7-Alkoxy-4-phenylamino-3-quinolinecar-bonitriles as Dual Inhibitors of Src and Abl Kinases

  摘要：

  We previously reported that several 7-alkoxy-4-phenylamino-3-quinolinecarbonitriles were potent inhibitors of Src kinase activity. We disclose here a new highly efficient and versatile route to these compounds, which are also potent inhibitors of Abl kinase.

  DOI：

  10.1021/jm0499458

文献信息

• Process for preparation of 4-amino-3-quinolinecarbonitriles
  申请人：Sutherland Wiggins Karen

  公开号：US20050043537A1

  公开（公告）日：2005-02-24

  This invention discloses a process for the preparation of a 4-amino-3-quinolinecarbonitrile comprising combining an amine compound with a cyanoacetic acid and an acid catalyst to yield a cyanoacetamide; condensing the cyanoacetamide with an optionally up to tetra-substituted aniline in an alcoholic solvent and a trialkylorthoformate to yield a 3-amino-2-cyanoacrylamide; combining the 3-amino-2-cyanoacrylamide with phosphorus oxychloride in acetonitrile, butyronitrile, toluene or xylene, optionally in the presence of a catalyst to yield a 4-amino-3-quinolinecarbonitrile and also discloses a process for the preparation of a 7-amino-thieno[3,2-b]pyridine-6-carbonitrile comprising combining a disubstituted 3-amino thiophene with a cyanoacetamide and trialkylorthoformate in an alcoholic solvent to obtain a 3-amino-2-cyanoacrylamide; and combining the 3-amino-2-cyanoacrylamide with phosphorus oxychloride and acetonitrile, butyronitrile, toluene or xylene, optionally in the presence of a catalyst to yield a 7-amino-thieno[3,2-b]pyridine-6-carbonitrile and also discloses a process for the preparation of a 4-amino-3-quinolinecarbonitrile by combining an amine compound with a cyanoacetic acid and a peptide coupling reagent to obtain a suspension; filtering the suspension to yield a cyanoacetamide; condensing the cyanoacetamide with an optionally up to tetra-substituted aniline, an alcoholic solvent, and triethylorthoformate to yield a 3-amino-2-cyanoacrylamide; and combining the 3-amino-2-cyanoacrylamide with phosphorus oxychloride to yield a 4-amino-3-quinolinecarbonitrile.

  这项发明揭示了一种制备4-氨基-3-喹啉碳腈的过程，包括将胺化合物与氰乙酸和酸催化剂结合以产生氰乙酰胺；将氰乙酰胺与醇溶剂和三烷基正甲酸酯中的一个或多个取代苯胺缩合以产生3-氨基-2-氰基丙烯酰胺；将3-氨基-2-氰基丙烯酰胺与氯化磷在乙腈、丁腈、甲苯或二甲苯中结合，可选地在催化剂存在的情况下以产生4-氨基-3-喹啉碳腈，并且还揭示了一种制备7-氨基噻吩[3,2-b]吡啶-6-碳腈的过程，包括将二取代的3-氨基噻吩与氰乙酰胺和三烷基正甲酸酯在醇溶剂中结合以获得3-氨基-2-氰基丙烯酰胺；将3-氨基-2-氰基丙烯酰胺与氯化磷和乙腈、丁腈、甲苯或二甲苯结合，可选地在催化剂存在的情况下以产生7-氨基噻吩[3,2-b]吡啶-6-碳腈，并且还揭示了一种通过将胺化合物与氰乙酸和肽偶联试剂结合以获得悬浮液；过滤悬浮液以产生氰乙酰胺；将氰乙酰胺与一个或多个取代苯胺、醇溶剂和三乙基正甲酸酯缩合以产生3-氨基-2-氰基丙烯酰胺；将3-氨基-2-氰基丙烯酰胺与氯化磷结合以产生4-氨基-3-喹啉碳腈的制备过程。
• [EN] 4-ANILINO-3-QUINOLINECARBONITRILES FOR THE TREATMENT OF CHRONIC MYELOGENOUS LEUKEMIA (CML)<br/>[FR] 4-ANILINO-3-QUINOLINECARBONITRILES DESTINES AU TRAITEMENT DE LEUCEMIE MYELOGENE CHRONIQUE (CML)
  申请人：WYETH CORP

  公开号：WO2005047259A1

  公开（公告）日：2005-05-26

  Compounds of the formula (I): wherein: n is an integer from 0-3; X is N, CH; R is alkyl of 1 to 3 carbon atoms; R' is 2,4-diCl, 5-OMe in para, ortho, or meta position; 2,4-diCl in para position; 3,4,5­tri-OMe in para position; 2-Cl, 5-OMe in para position; 2-Me, 5-OMe in para position; 2,4-di-Me in para position; 2,4-diMe-5-OMe in para position; 2,4-diCl, 5-OEt in para position; and R2 is alkyl of 1 to 3 carbon atoms, and pharmaceutically acceptable salts thereof.

  式(I)的化合物：其中：n是0-3之间的整数；X是N，CH；R是1至3个碳原子的烷基；R'是对位、邻位或间位的2,4-二氯，5-甲氧基；对位的2,4-二氯；对位的3,4,5-三甲氧基；对位的2-氯，5-甲氧基；对位的2-甲基，5-甲氧基；对位的2,4-二甲基；对位的2,4-二甲基-5-甲氧基；对位的2,4-二氯，5-乙氧基；以及R2是1至3个碳原子的烷基，及其药用可接受的盐。
• Process for the preparation of 7-substituted-3 quinolinecarbonitriles
  申请人：Wyeth Holdings Corporation

  公开号：US20030212276A1

  公开（公告）日：2003-11-13

  There is provided a process for the preparation of 7-substituted-3-quinolinecarbonitriles and intermediates useful in a process to prepare 7-substituted-3-quinolinecarbonitriles and pharmaceutically acceptable salts is described. Where 7-fluoro-4-oxo-1,4-dihydro-3-quinolinecarbonitrile is converted in three steps to 7-substituted-3-quinolinecarbonitriles which inhibit the action of certain protein kinases and are useful in the treatment of cancer.

  提供了一种制备7-取代-3-喹啉羰基腈和中间体的方法，该中间体在制备7-取代-3-喹啉羰基腈和药用可接受盐的过程中有用。将7-氟-4-氧代-1,4-二氢-3-喹啉羰基腈转化为7-取代-3-喹啉羰基腈，经过三个步骤，这些化合物抑制某些蛋白激酶的作用，并在癌症治疗中有用。
• [EN] HETEROCYCLIC COMPOUNDS, METHODS OF SYNTHESIS AND USES THEREOF<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES, LEURS MÉTHODES DE SYNTHÈSE ET LEURS UTILISATIONS
  申请人：AGENCY SCIENCE TECH & RES

  公开号：WO2017135901A1

  公开（公告）日：2017-08-10

  The present invention relates to 3-quinolinecarbonitrile compounds of formula (I) disclosed herein, methods for their synthesis, and uses thereof. Advantageously, the disclosed heterocyclic compounds may demonstrate enhanced efficacy in antitumor properties. Hence, the present disclosure also relates to the use of the disclosed 3-quinolinecarbonitrile compounds or pharmaceutical compositions thereof in cancer treatment.

  本发明涉及本文所披露的式（I）的3-喹啉碳腈化合物，其合成方法和用途。有益的是，所披露的杂环化合物可能表现出在抗肿瘤性能方面的增强效果。因此，本公开还涉及在癌症治疗中使用所披露的3-喹啉碳腈化合物或其制剂。
• 3-Quinolinecarbonitrile protein kinase inhibitors
  申请人：Berger Maarten Dan

  公开号：US20050187247A1

  公开（公告）日：2005-08-25

  This invention provides a compound of Formula 1 where Ar, X, R 1 , R 2 , R 3 , and R 4 are defined herein, or a pharmaceutically acceptable salt thereof useful in the prevention or inhibition of diseases associated with the Ras/Raf/MEK signaling cascade in a mammal, such as neoplasms, strokes, osteoporosis, cancer, rheumatoid arthritis, inflammatory disease, polycystic kidney disease, and colonic polyps, and methods of making the compounds of formula 1 and intermediates.

  该发明提供了一种化合物，其化学式为1，其中Ar、X、R1、R2、R3和R4的定义如下，或其药用盐，在哺乳动物体内用于预防或抑制与Ras/Raf/MEK信号级联相关的疾病，如肿瘤、中风、骨质疏松症、癌症、类风湿性关节炎、炎症性疾病、多囊性肾病和结肠息肉，以及制备化合物1和中间体的方法。